Stiripentol for the treatment of refractory status epilepticus.
Epilepsy
Status epilepticus
Stiripentol
Journal
Neurological research and practice
ISSN: 2524-3489
Titre abrégé: Neurol Res Pract
Pays: England
ID NLM: 101767802
Informations de publication
Date de publication:
21 Oct 2024
21 Oct 2024
Historique:
received:
24
04
2024
accepted:
02
10
2024
medline:
21
10
2024
pubmed:
21
10
2024
entrez:
20
10
2024
Statut:
epublish
Résumé
Status epilepticus (SE) is one of the most common neurological emergencies and an acutely life-threatening condition characterized by high mortality and morbidity. Despite the well-established staged therapy of status epilepticus, especially stages 1 and 2, more than one third of patients develop (super-) refractory SE. Despite a large variety of potential treatment options for super-refractory SE, there is an unmet clinical need of potential new treatment ideas in this often desperate clinical situation. A number of studies have demonstrated the safety and efficacy of stiripentol (STP) in patients with Dravet syndrome (DS) and in children with focal epilepsy and generalized epilepsies. Some smaller series and case reports have documented the use of STP in the treatment of status epilepticus in adult patients. We retrospectively analyzed all patients who were admitted to the Department of Neurology at Marburg University Hospital between 2013 and 2023 with a diagnosis of (super)-refractory status epilepticus and who received additional treatment of SE with STP. All patients who received STP during the SE were included, regardless of previous medication. SE ceased in 64% of 25 patients (13 female and 12 male). The mean age was 58.6 ± 21.9 years (mean ± SD). 72% had a structural epilepsy. In 20% of patients, SE was terminated by the administration of STP alone in 32% of cases, while in a further 32% of patients, the simultaneous administration of multiple anti-seizure medications (ASMs) including STP was potentially responsible for the cessation of the SE, with valproic acid (VPA), benzodiazepines and STP, being the most frequently implicated ASMs. In 12% of patients, there was at least a temporary improvement in the electroencephalogram (EEG). Stiripentol had to be discontinued in three cases due to a reduction in vigilance or hypercalcemia. Stiripentol may represent a promising additional treatment option for refractory and super-refractory status epilepticus. The tolerability of this treatment has already been demonstrated in previous studies, and was also reflected in these data. Further prospective investigation in larger patient populations are necessary to ascertain the efficacy of stiripentol in SE. NCT06540378, retrospectively registered.
Sections du résumé
BACKGROUND
BACKGROUND
Status epilepticus (SE) is one of the most common neurological emergencies and an acutely life-threatening condition characterized by high mortality and morbidity. Despite the well-established staged therapy of status epilepticus, especially stages 1 and 2, more than one third of patients develop (super-) refractory SE. Despite a large variety of potential treatment options for super-refractory SE, there is an unmet clinical need of potential new treatment ideas in this often desperate clinical situation. A number of studies have demonstrated the safety and efficacy of stiripentol (STP) in patients with Dravet syndrome (DS) and in children with focal epilepsy and generalized epilepsies. Some smaller series and case reports have documented the use of STP in the treatment of status epilepticus in adult patients.
METHODS
METHODS
We retrospectively analyzed all patients who were admitted to the Department of Neurology at Marburg University Hospital between 2013 and 2023 with a diagnosis of (super)-refractory status epilepticus and who received additional treatment of SE with STP. All patients who received STP during the SE were included, regardless of previous medication.
RESULTS
RESULTS
SE ceased in 64% of 25 patients (13 female and 12 male). The mean age was 58.6 ± 21.9 years (mean ± SD). 72% had a structural epilepsy. In 20% of patients, SE was terminated by the administration of STP alone in 32% of cases, while in a further 32% of patients, the simultaneous administration of multiple anti-seizure medications (ASMs) including STP was potentially responsible for the cessation of the SE, with valproic acid (VPA), benzodiazepines and STP, being the most frequently implicated ASMs. In 12% of patients, there was at least a temporary improvement in the electroencephalogram (EEG). Stiripentol had to be discontinued in three cases due to a reduction in vigilance or hypercalcemia.
CONCLUSIONS
CONCLUSIONS
Stiripentol may represent a promising additional treatment option for refractory and super-refractory status epilepticus. The tolerability of this treatment has already been demonstrated in previous studies, and was also reflected in these data. Further prospective investigation in larger patient populations are necessary to ascertain the efficacy of stiripentol in SE.
TRIAL REGISTRATION
BACKGROUND
NCT06540378, retrospectively registered.
Identifiants
pubmed: 39428490
doi: 10.1186/s42466-024-00348-x
pii: 10.1186/s42466-024-00348-x
doi:
Banques de données
ClinicalTrials.gov
['NCT06540378']
Types de publication
Journal Article
Langues
eng
Pagination
49Informations de copyright
© 2024. The Author(s).
Références
Auvin, S., & Dupuis, N. (2014). Outcome of status epilepticus. What do we learn from animal data? Epileptic Disorders, 16(s1), S37–S43. https://doi.org/10.1684/epd.2014.0670
doi: 10.1684/epd.2014.0670
Balestrini, S., Doccini, V., Boncristiano, A., Lenge, M., De Masi, S., & Guerrini, R. (2022). Efficacy and safety of long-term treatment with stiripentol in children and adults with drug-resistant epilepsies: A retrospective cohort study of 196 patients. Drugs—Real World Outcomes, 9(3), 451–461. https://doi.org/10.1007/s40801-022-00305-7
doi: 10.1007/s40801-022-00305-7
pmcid: 9392664
Brigo, F., Igwe, S. C., & Bragazzi, N. L. (2020). Stiripentol add-on therapy for drug-resistant focal epilepsy. Cochrane Database of Systematic Reviews, 5(5), CD009887. https://doi.org/10.1002/14651858.CD009887.pub5
doi: 10.1002/14651858.CD009887.pub5
Brigo, F., Igwe, S. C., & Bragazzi, N. L. (2022). Stiripentol add-on therapy for drug-resistant focal epilepsy. Cochrane Database of Systematic Reviews, 2022(9), CD009887. https://doi.org/10.1002/14651858.CD009887.pub6
doi: 10.1002/14651858.CD009887.pub6
pmcid: 9447417
Chen, J. W., & Wasterlain, C. G. (2006). Status epilepticus: Pathophysiology and management in adults. The Lancet Neurology, 5(3), 246–256. https://doi.org/10.1016/S1474-4422(06)70374-X
doi: 10.1016/S1474-4422(06)70374-X
European Medicines Agency (Hg.) (2017): Diacomit. Online verfügbar unter https://www.ema.europa.eu/en/medicines/human/EPAR/diacomit .
Grosenbaugh, D. K., & Mott, D. D. (2013). Stiripentol in refractory status epilepticus. Epilepsia, 54(s6), S103–S105. https://doi.org/10.1111/epi.12291
doi: 10.1111/epi.12291
Habermehl, L., Mross, P. M., Krause, K., Immisch, I., Chiru, D., Zahnert, F., et al. (2021). Stiripentol in the treatment of adults with focal epilepsy- a retrospective analysis. Seizure, 88, 7–11. https://doi.org/10.1016/j.seizure.2021.03.019
doi: 10.1016/j.seizure.2021.03.019
Kantanen, A.-M., Reinikainen, M., Parviainen, I., & Kälviäinen, R. (2017). Long-term outcome of refractory status epilepticus in adults: A retrospective population-based study. Epilepsy research, 133, 13–21. https://doi.org/10.1016/j.eplepsyres.2017.03.009
doi: 10.1016/j.eplepsyres.2017.03.009
Roberg, L. E., Monsson, O., Kristensen, S. B., Dahl, S. M., Ulvin, L. B., Heuser, K., Taubøll, E., Strzelczyk, A., Knake, S., Bechert, L., Rosenow, F., Beier, D., Beniczky, S., Krøigård, T., & Beier, C. P. (2022). Prediction of long-term survival after status epilepticus using the ACD score. JAMA Neurology, 79(6), 604–613. https://doi.org/10.1001/jamaneurol.2022.0609
doi: 10.1001/jamaneurol.2022.0609
pmcid: 9002715
Rosati, A., Boncristiano, A., Doccini, V., Pugi, A., Pisano, T., Lenge, M., De Masi, S., & Guerrini, R. (2019). Long‐term efficacy of add‐on stiripentol treatment in children, adolescents, and young adults with refractory epilepsies: A single center prospective observational study. Epilepsia, 60(11), 2255–2262. https://doi.org/10.1111/epi.16363
doi: 10.1111/epi.16363
Sculier, C., Gaínza-Lein, M., Sánchez Fernández, I., & Loddenkemper, T. (2018). Long-term outcomes of status epilepticus: A critical assessment. Epilepsia, 59, 155–169. https://doi.org/10.1111/epi.14515
doi: 10.1111/epi.14515
pmcid: 6221081
Strzelczyk, A., Kortland, L. M., Knake, S., & Rosenow, F. (2015). Stiripentol for the treatment of super-refractory status epilepticus. Acta Neurologica Scandinavica., 132(6), 435–439. https://doi.org/10.1111/ane.12403
doi: 10.1111/ane.12403
Tian, L., Li, Y., Xue, X., Wu, M., Liu, F., Hao, X., & Zhou, D. (2015). Super-refractory status epilepticus in W est C hina. Acta Neurologica Scandinavica, 132(1), 1–6. https://doi.org/10.1111/ane.12336
doi: 10.1111/ane.12336
Uchida, Y., Terada, K., Madokoro, Y., Fujioka, T., Mizuno, M., Toyoda, T., Kato, D., & Matsukawa, N. (2018). Stiripentol for the treatment of super-refractory status epilepticus with cross-sensitivity. Acta Neurologica Scandinavica., 137(4), 432–437. https://doi.org/10.1111/ane.12888
doi: 10.1111/ane.12888